CN105218506A - A kind of method being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne - Google Patents
A kind of method being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
Abstract
The invention provides a kind of method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne.The method is carried out under nitrogen atmosphere, uses copper catalyst, alkali reagent, directly with o-Halogen benzoic acids methyl esters and terminal alkyne compound for raw material synthesizes Isocoumarin compounds.The method uses raw material cheap and easy to get and copper catalyst, do not use the special reaction conditions such as part, acid, superoxide, microwave radiation, substrate does not need pre-functionalization, reaction conditions is gentle, simple to operate, the selectivity of product and productive rate are all very high, pharmaceutically have potential application prospect.
Description
[technical field]
The present invention relates to organic synthesis and field of medicaments, be specifically related to a kind of method being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne.
[background technology]
Isocoumarin is the hexa-atomic lactone compound of benzo, and it is the natural lactone compound that a class is widespread in nature, and the derivative of this compounds has antibacterial, antianaphylaxis, AntiHIV1 RT activity and the multiple pharmacologically active such as antitumor.Such as, 3-phenyl Isocoumarin can resist the growth and breeding of the multiple fungies such as palace portion cochliobolus (Cochliobolusmiyabeanus), shipping rod method (Alternariamaritima), Stem of Lovely Achnatherum sickle-like bacteria (Fusariumsplendens) and Gibberella zeae (Giberellazeae) effectively; The restraining effect of 3-(4-hydroxy phenyl) Isocoumarin to Stem of Lovely Achnatherum sickle-like bacteria (Fusariumsplendens) is stronger; Isocoumarin NM-3 can resist people's multiple myeloma cells.Isocoumarin compounds not only has excellent biological activity and also has changeable chemical structure, is one of focus of organic synthesis and pharmaceutical chemistry research, and the exploration about this kind of compou nd synthesis route is also constantly being goed deep into.
At present, existing a large amount of documents is through reporting the synthetic method of Isocoumarin compounds.Traditional method is obtained by the close electrocyclization of adjacent alkynyl benzoic acid derivative, but obtaining adjacent alkynyl benzoic acid derivative needs to use expensive palladium catalyst and excessive alkynes, and productive rate is not high.Recent two decades has developed new synthetic method, the carbonylation reaction of the adjacent iodine benzalkonium ketone of the palladium chtalyst as report in 1994 or α-(adjacent halogen aryl)-replacement ketone compounds, within 2008, report the high phthalic acid of microwave participation and the reaction of acyl chlorides or ester class, within 2011, YounSW reports the dioxide giving reaction of NHC catalysis 2-alkynyl phenyl aldehyde, it is that substrate catalyzes and synthesizes the method for Isocoumarin through copper that the people such as XiCJ in 2012 report with 2-halogenated benzoic acid and derivative thereof and 1,3-diketone.Recently, the people such as AidhenIS report the isocumarans compound being synthesized the replacement of 3-aryl by 2-(brooethyl) methyl benzoate two step, but these reactions mostly are polystep reaction, and the selectivity of product is low, or substrate needs functionalization in advance, and severe reaction conditions.
[reference: NapolitanoE.Org.Prep.Proced.Int.1997,29,631-664; SubramanianV, BatchuVR, BarangeD, PalM.J.Org.Chem.2005,70,4778-4783; KawanoT, AgataN, KharbandaS.CancerChemoth.Pharm.2007,59,329-335; PalS, ChatareV, PalM.Curr.Org.Chem.2011,15,782-800; GeZY, FeiXD, TangT, ZhuYM, ShenJK.J.Org.Chem.2012,77,5736-5743; FeiXD, GeZY, TangT, ZhuYM, ShenJK.J.Org.Chem.2012,77,10321-10328; SudarshanK, MannaMK, AidhenIS.Eur.J.Org.Chem.2015,1797-1803.]
For the deficiency of aforesaid method, develop with copper cheap and easy to get for catalyzer, directly use o-Halogen benzoic acids methyl esters and terminal alkyne to be raw material, reaction conditions is gentle, and productive rate is higher, simple to operate, synthesis new way applied widely, pharmaceutically has potential using value.
[summary of the invention]
The object of the invention is exploitation one under nitrogen atmosphere, use copper catalyst, alkali reagent, with o-Halogen benzoic acids methyl esters and terminal alkyne compound for raw material, the method for high conversion and high productivity synthesis Isocoumarin compounds.
Goal of the invention of the present invention is achieved by the following technical solution:
A kind of structural formula is
the preparation method of Isocoumarin compounds, comprise following steps:
Get o-Halogen benzoic acids methyl compound, terminal alkyne compound, copper catalyst, alkali reagent, solvent be placed in reaction vessel, mixing; Under nitrogen atmosphere, at temperature of reaction is 80 ~ 120 DEG C, Keep agitation reaction 15 ~ 30h, is cooled to room temperature after reaction terminates, with saturated ammonium chloride solution washing, then use organic solvent extraction, dry, underpressure distillation is concentrated except desolventizing, and thick product, through pillar layer separation, obtains target product.
In described general formula I, R
1h, F, CH
3; R
2aryl, fatty group.
In above-mentioned synthetic method, described copper catalyst is selected from least one in cuprous iodide, cuprous bromide, cuprous chloride, cupric bromide.
In above-mentioned synthetic method, described alkali reagent is at least one in sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert.-butoxide.
In above-mentioned synthetic method, described o-Halogen benzoic acids methyl compound is selected from o-bromobenzoic acid methyl esters, o-iodobenzoic acid methyl esters, the bromo-methyl 4 methylbenzoate of 2-, the bromo-4-fluorophenyl carbamate of 2-.
In above-mentioned synthetic method, described terminal alkyne compound be selected from phenylacetylene, 2-ethynyl toluene, to tert.-butylbenzene ethyl-acetylene, 4-acetylenylaniline, 4-acetylenylbenzene methyl ether, 4-fluorobenzene acetylene, 1-ethynyl naphthalene, 1-octyne, 3,3-diformazans-ethyl acetylene, cyclohexyl-acetylene, 3-cyclohexyl-1-propine, 5-phenyl-1-pentyne.
In above-mentioned synthetic method, in described reaction process, solvent for use is selected from least one in Isosorbide-5-Nitrae-dioxane, DMF (DMF), acetonitrile, dimethyl sulfoxide (DMSO).
In above-mentioned synthetic method, described copper catalyst, alkali reagent, mol ratio between terminal alkyne compound and o-Halogen benzoic acids methyl compound are [0.05 ~ 0.2]: [1.0 ~ 3.0]: 1:[1.0 ~ 1.5].Temperature of reaction is 80 ~ 120 DEG C, and the reaction times is 15 ~ 30h.
In above-mentioned synthetic method, the organic solvent in described extraction step is at least one in ethyl acetate, trichloromethane or methylene dichloride.
Experimentally result, a kind of method directly being prepared Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne one step provided by the present invention.The features such as the method has copper catalyst and cheaper starting materials is easy to get, terminal alkyne kind used is many, gained target product is easily separated, productive rate is high, operation is simple, suitability is wide.To this method solve in other synthetic methods existing low-yield, low selectivity, complicated operation, valuable catalyst such as to mix at the problem.
[Brief Description Of Drawings]
Fig. 1 is the reaction formula being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne.
[embodiment]
Be described further synthetic method of the present invention below in conjunction with synthesis example of the present invention, it should be noted that, embodiment does not form the restriction to application claims protection domain.
As shown in Figure 1, the synthesis step synthesizing Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne provided by the invention is: o-Halogen benzoic acids methyl ester agent (mol ratio 100 ~ 150% is based on terminal alkyne reagent), terminal alkyne reagent, copper catalyst (mol ratio 5 ~ 20% is based on terminal alkyne reagent), alkali reagent (mol ratio 100 ~ 300% is based on terminal alkyne reagent), organic solvent are placed in reaction vessel, mixing; Under nitrogen atmosphere, at temperature of reaction is 80 ~ 120 DEG C, Keep agitation reaction 15 ~ 30h, be cooled to room temperature after reaction terminates, with saturated ammonium chloride solution washing, then use organic solvent extraction, dry, underpressure distillation is concentrated except desolventizing, and thick product, through pillar layer separation, obtains Isocoumarin compounds.
Synthesis example 1
The synthesis of 3-phenyl Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol phenylacetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 96%.
1HNMR(400MHz,CDCl
3):δ8.31(d,J＝8.1Hz,1H),7.88(d,J＝6.7Hz,2H),7.72(t,J＝7.6Hz,1H),7.51-7.40(m,5H),6.96(s,1H)。
Synthesis example 2
The synthesis of 3-(2-tolyl) Isocoumarin
Add 0.20mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol2-ethynyl toluene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 85%.
1HNMR(400MHz,CDCl
3):δ8.31(d,J＝7.9Hz,1H),7.72(t,J＝7.5Hz,1H),7.54-7.44(m,3H),7.33(t,J＝7.4Hz,1H),7.30-7.20(m,2H),6.60(s,1H),2.50(s,3H)。
Synthesis example 3
The synthesis of 3-(4-tert-butyl-phenyl) Isocoumarin
Add 0.24mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol to tert.-butylbenzene ethyl-acetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 95%.
1HNMR(400MHz,CDCl
3):δ8.30(d,J＝7.9Hz,1H),7.82(d,J＝8.4Hz,2H),7.70(m,1H),7.49-7.44(m,3H),6.92(s,1H),1.35(s,9H)。
Synthesis example 4
The synthesis of 3-(4-aminophenyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol4-acetylenylaniline, 0.02mmol cuprous iodide, 0.50mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 80%.
1HNMR(400MHz,CDCl
3):δ8.27(d,J＝7.9Hz,1H),7.70-7.65(m,3H),7.44-7.40(m,2H),6.83-6.63(m,3H),3.93(s,2H)。
Synthesis example 5
The synthesis of 3-(4-methoxyphenyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol4-acetylenylbenzene methyl ether, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 110 DEG C, Keep agitation 20h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 78%.
1HNMR(400MHz,CDCl
3):δ8.29(d,J＝8.1Hz,1H),7.83(d,J＝8.9Hz,2H),7.70(t,J＝7.6Hz,1H),7.50-7.42(m,2H),6.97(d,J＝8.9Hz,2H),6.84(s,1H),3.87(s,3H)。
Synthesis example 6
The synthesis of 3-(4-fluorophenyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol4-fluorobenzene acetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 19h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 73%.
1HNMR(400MHz,CDCl
3):δ8.31(d,J＝7.9Hz,1H),7.88(dd,J＝8.8,5.3Hz,2H),7.73(t,J＝7.5Hz,1H),7.51(t,J＝8.0Hz,2H),7.16(t,J＝8.6Hz,2H),6.89(s,1H)。
Synthesis example 7
The synthesis of 3-(2-naphthyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol2-ethynyl naphthalene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 87%.
1HNMR(400MHz,CDCl
3):δ8.38(m,1H),8.24(m,1H),8.01-7.87(m,2H),7.82-7.70(m,2H),7.59-7.51(m,5H),6.81(s,1H)。
Synthesis example 8
The synthesis of 3-n-hexyl Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol1-octyne, 0.02mmol cuprous chloride, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 70%.
1HNMR(400MHz,CDCl
3):δ8.24(d,J＝7.9Hz,1H),7.66(t,J＝7.5Hz,1H),7.44(t,J＝7.6Hz,1H),7.34(d,J＝7.8Hz,1H),6.24(s,1H),2.51(t,J＝7.6Hz,2H),1.76-1.64(m,2H),1.43-1.22(m,6H),0.88(t,J＝6.4Hz,3H)。
Synthesis example 9
The synthesis of 3-tertiary butyl Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol3,3-diformazan-ethyl acetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 20h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 86%.
1HNMR(400MHz,CDCl
3):δ8.24(d,J＝7.9Hz,1H),7.66(t,J＝7.5Hz,1H),7.44(t,J＝7.6Hz,1H),7.37(d,J＝7.9Hz,1H),6.30(s,1H),1.32(s,9H)。
Synthesis example 10
The synthesis of 3-cyclohexyl Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol cyclohexyl-acetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 84%.
1HNMR(400MHz,CDCl
3):δ8.22(d,J＝7.9Hz,1H),7.64(t,J＝7.6Hz,1H),7.42(t,J＝7.6Hz,1H),7.34(d,J＝7.8Hz,1H),6.21(s,1H),2.42(t,J＝11.4Hz,1H),2.02-1.99(m,2H),1.84-1.81(m,2H),1.52-1.07(m,6H)。
Synthesis example 11
The synthesis of 3-(cyclohexyl methyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol3-cyclohexyl-1-propine, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 86%.
1HNMR(400MHz,CDCl
3):δ8.24(d,J＝7.9Hz,1H),7.66(t,J＝7.5Hz,1H),7.44(t,J＝7.6Hz,1H),7.34(d,J＝7.9Hz,1H),6.22(s,1H),2.38(d,J＝7.0Hz,2H),1.89-1.62(m,6H),1.29(m,1H),1.21-1.07(m,2H),1.03-0.86(m,2H)。
Synthesis example 12
The synthesis of 3-(3-phenyl propyl) Isocoumarin
Add 0.22mmol o-bromobenzoic acid methyl esters in the reactor, 0.20mmol5-phenyl-1-pentyne, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 95%.
1HNMR(400MHz,CDCl
3):δ8.25(d,J＝7.9Hz,1H),7.66(t,J＝7.6Hz,1H),7.44(t,J＝7.6Hz,1H),7.34(d,J＝7.9Hz,1H),7.28(dd,J＝14.3,7.1Hz,2H),7.21-7.17(m,3H),6.24(s,1H),2.71(t,J＝7.6Hz,2H),2.55(t,J＝7.6Hz,2H),2.14-2.00(m,2H)。
Synthesis example 13
The synthesis of 6-methyl-3-phenyl Isocoumarin
Add the bromo-methyl 4 methylbenzoate of 0.22mmol2-in the reactor, 0.20mmol phenylacetylene, 0.01mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 100 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 86%.
1HNMR(400MHz,CDCl
3):δ8.19(d,J＝8.0Hz,1H),7.87(d,J＝7.6Hz,2H),7.50-7.39(m,3H),7.34-7.27(m,2H),6.89(s,1H),2.49(s,3H)。
Synthesis example 14
The synthesis of 6-fluoro-3-phenyl Isocoumarin
Add the bromo-4-fluorophenyl carbamate of 0.22mmol2-in the reactor, 0.20mmol phenylacetylene, 0.02mmol cuprous iodide, 0.40mmol sodium hydroxide, 1.0mL acetonitrile solvent.Under nitrogen atmosphere, be heated to 110 DEG C, Keep agitation 24h, stopped reaction, is cooled to room temperature, adds saturated ammonium chloride solution washing, and with dichloromethane extraction, dry, underpressure distillation is except desolventizing, and namely thick product obtains target product through pillar layer separation, productive rate 89%.
1HNMR(400MHz,CDCl
3):δ8.31(dd,J＝8.0,6.0Hz,1H),7.86(d,J＝5.8Hz,2H),7.45(d,J＝5.4Hz,3H),7.22-7.11(m,2H),6.89(s,1H)。
Claims (8)
1. synthesized a method for Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne, comprise following step:
Get o-Halogen benzoic acids methyl compound, terminal alkyne compound, copper catalyst, alkali reagent, solvent be placed in reaction vessel, mixing; Under nitrogen atmosphere, at temperature of reaction is 80 ~ 120 DEG C, Keep agitation reaction 20 ~ 30h, be cooled to room temperature after reaction terminates, with saturated ammonium chloride solution washing, then use organic solvent extraction, dry, underpressure distillation is concentrated except desolventizing, and thick product, through pillar layer separation, obtains Isocoumarin compounds.There is following structural formula:
In described general formula I, R
1h, F, CH
3; R
2aryl, fatty group.
2. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, is characterized in that, described copper catalyst is selected from least one in cuprous iodide, cuprous bromide, cuprous chloride, cupric bromide.
3. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, is characterized in that, described alkali reagent is at least one in sodium hydroxide, potassium hydroxide, sodium tert-butoxide, potassium tert.-butoxide.
4. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, it is characterized in that, described o-Halogen benzoic acids methyl compound is selected from o-bromobenzoic acid methyl esters, o-iodobenzoic acid methyl esters, the bromo-methyl 4 methylbenzoate of 2-, the bromo-4-fluorophenyl carbamate of 2-.
5. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, it is characterized in that, described terminal alkyne compound be selected from phenylacetylene, 2-ethynyl toluene, to tert.-butylbenzene ethyl-acetylene, 4-acetylenylaniline, 4-acetylenylbenzene methyl ether, 4-fluorobenzene acetylene, 1-ethynyl naphthalene, 1-octyne, 3,3-diformazans-ethyl acetylene, cyclohexyl-acetylene, 3-cyclohexyl-1-propine, 5-phenyl-1-pentyne.
6. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, it is characterized in that, in described reaction process, solvent for use is selected from 1, at least one in 4-dioxane, DMF (DMF), acetonitrile, dimethyl sulfoxide (DMSO).
7. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, it is characterized in that, copper catalyst, alkali reagent, mol ratio between terminal alkyne compound and o-Halogen benzoic acids methyl compound are [0.05 ~ 0.2]: [1.0 ~ 3.0]: 1:[1.0 ~ 1.5].Temperature of reaction is 80 ~ 120 DEG C, and the reaction times is 15 ~ 30h.
8. method of being synthesized Isocoumarin compounds by o-Halogen benzoic acids methyl esters and terminal alkyne according to claim 1, is characterized in that, the organic solvent in described extraction step is at least one in ethyl acetate, trichloromethane or methylene dichloride.
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| CN107641110A (en) * | 2016-07-29 | 2018-01-30 | 浙江工业大学 | A kind of method for synthesizing isocoumarin class compound |
| CN106588851A (en) * | 2016-11-29 | 2017-04-26 | 南阳师范学院 | Method of synthesizing isocoumarin derivatives by catalyzing tandem reaction in water phase |
| CN106588767A (en) * | 2016-11-29 | 2017-04-26 | 南阳师范学院 | Method of catalyzing tandem reaction to synthesize isoquinolinone derivative in water phase |
| CN106588767B (en) * | 2016-11-29 | 2019-07-26 | 南阳师范学院 | A method of tandem reaction, which is catalyzed, in water phase synthesizes isoquinolinone derivatives |
| CN107973768A (en) * | 2017-12-19 | 2018-05-01 | 江苏欣诺科催化剂有限公司 | The method of one-step synthesis coumarin kind compound |
| CN107973768B (en) * | 2017-12-19 | 2020-11-10 | 江苏欣诺科催化剂有限公司 | Method for synthesizing coumarin compound in one step |
| CN112625020A (en) * | 2019-09-24 | 2021-04-09 | 南开大学 | Synthesis of isocoumarin derivative by carbon-hydrogen bond activation reaction under catalysis of rhodium |
| CN112625020B (en) * | 2019-09-24 | 2022-12-13 | 南开大学 | Synthesis of isocoumarin derivative by carbon-hydrogen bond activation reaction under catalysis of rhodium |
| CN115785052A (en) * | 2022-11-21 | 2023-03-14 | 河南大学 | Method for synthesizing isocoumarin with high selectivity under catalysis of polyacid |
| CN115785052B (en) * | 2022-11-21 | 2024-01-26 | 河南大学 | Method for synthesizing isocoumarin with high selectivity under catalysis of polyacid |
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